Microscopic changes with acetic acid and sodium hydroxide in the rabbit low-volume eye test

Differences in ocular irritancy have been hypothesized to reflect differenc es in the extent of initial injury. Although differences in the processes l eading to tissue damage may exist, extent of injury is believed to be the p rincipal factor determining final outcome of ocular irritation. Previous st udies characterizing the pathology of surfactant-induced ocular irritation support this premise. The purpose of this study was to begin to determine t he applicability of this premise in terms of nonsurfactants; we planned to accomplish this by assessing the ocular irritancy of different concentratio ns of an acid and an alkali. Ten microliters of 3 or 10% acetic acid (C2H4O 2) or 2 or 8% sodium hydroxide (NaOH) were directly applied to the cornea o f the right eye of each test rabbit. Untreated left eyes served as the cont rols. Eyes and eyelids were macroscopically examined for signs of irritatio n beginning 3 hours after dosing and periodically until recovery or day 35. Eyes and eyelids from animals in each group were collected for microscopic examination after 3 hours and on days 1, 3, and 35. The macroscopic and mi croscopic changes were consistent with slight (3% C2H4O2), mild (2% NaOH, 1 0% C2H4O2), and severe (8% NaOH) irritancy. The spectra of changes were sim ilar to those previously reported for surfactants of differing types and ir ritancies. As with surfactants, as the extent of initial injury increased, the intensity and duration of the subsequent responses increased. These res ults indicate that our hypothesis also applies to nonsurfactants. The resul ts also support our belief that the initial extent of injury associated wit h ocular irritation may be used to predict the subsequent responses and fin al outcome. Finally, our results further indicate that such an approach may be applicable to the development of alternative assays that are based on e ither injury to ex vivo eyes or injury to an in vitro corneal equivalent sy stem.